• BMB Reports
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• 제31권3호
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• pp.245-248
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• 1998

Human epidermoid carcinoma A431 cells have an extraordinarily large number of epidermal growth factor (EGF) receptors, and their growth is inhibited by EGF, which results in growth arrest at the Gl phase. In order to investigate the EGF-mediated inhibition mechanism, the expression level of DNA topoisomerase (topo) II was analyzed after EGF treatment. As a result, it was shown that EGF treatment lowered the amount of 170 kDa topo II (topo $II{\alpha}$) but not 180 kDa (topo $II{\beta}$). However, the A431 cell variant resistant to EGF was not sensitive to EGF treatment. These results suggest that EGF-induced growth arrest of A431 cells may be closely related to the depletion of topo $II{\alpha}$.

• 한국산학기술학회논문지
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• 제21권9호
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• pp.559-568
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• 2020

세포 분열 및 성장 촉진에 영향을 주는 상피세포 성장인자(Epidermal Growth Factor, EGF)는 다양한 의학적 용도를 갖고 있는 호르몬 단백질이다. 본 연구에서는 human EGF 유전자를 대장균 코돈에 최적화 하고 pRSET 벡터에 클로닝하여 발현벡터를 구축하였다. Human EGF를 봉입체가 아닌 활성이 있는 형태로의 과량 발현을 위해 코돈의 최적화와 더불어 최초로 샤페론 공발현이 시도되었다. 발현된 Native protein 형태의 재조합 human EGF는 고순도로 정제하기 위해 Ion Exchange Chromatography를 2번 연속적으로 수행하여 순수 분리 정제되었고, ELISA 분석결과 99% 이상으로 재조합 EGF의 활성도가 상업용 EGF와 유사하게 나타났으며, 세포증식시험 결과 인간 재조합 EGF는 인체 피부 섬유아세포의 세포증식을 촉진하는 것으로 확인 되었다. 본 연구의 인간 EGF 발현 시스템은 양적인 측면 뿐 아니라 성공적인 활성형태의 발현으로 추가적인 재접힘 과정 및 N 말단의 융합부분을 제거하기 위한 크로마토그래피 작업이 필요가 없다는 점에서 기존의 방법들에 대체 될 수 있는 효과적인 인간 EGF 발현 시스템을 제공하고 있다.

• 구강회복응용과학지
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• 제36권3호
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• pp.145-157
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• 2020

목적: 본 연구에서는 구강연조직재생에서 인간치은섬유아세포에 hydrophobically modified glycol chitosan (HGC) 기반 나노방출제어시스템을 적용 시 PI3K-AKT 신호전달의 세포생존 연관 유전자를 통해 trichloroacetic acid (TCA)와 epidermal growth factor (EGF)의 영향을 확인하고자 하였다. 연구 재료 및 방법: TCA와 EGF를 방출하는 나노방출제어시스템을 제작하였다. 실험군은 3가지 군으로 나누었다; 대조군(CON), TCA-담지형 나노방출제어시스템 투여군(EXP1), TCA-와 EGF- 담지형 나노방출제어시스템 투여군(EXP2). 인간치은섬유아세포 배양 후 PI3K-AKT 신호전달에 연관된 총 29개 유전자를 실시간 중합효소연쇄반응으로 분석했다. 일요인 분산분석 및 다중회귀분석이 사용되었다. 결과: 세포생존 관련 유전자들은 EXP1과 EXP2에서 상향조절되었다. 다중회귀분석에서는 ITGB1이 AKT1의 발현에 가장 영향력 있는 요소로 결정되었다. 결론: HGC기반 나노방출제어시스템을 통한 TCA와 EGF의 적용은 세포생존에 관한 신호전달을 상향 조절시킬 수 있다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권2호
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• pp.110-122
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• 2005

Adenoid cystic carcinoma (ACC) of salivary glands has a protracted clinical course with perineural invasion, delayed onset of hematogenous metastasis, and poor responses to classical cytotoxic chemotherapic agents. Most deaths from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the dissemination of metastatic cells is important for the design of more effective therapy of salivary cancer. I determined in vitro expression of epidermal growth factor receptor (EGFR) and its downstream effectors and vascular endothelial growth factor receptor (VEGFR)-2 on a human salivary ACC cell line (ACC2). I also evaluated the expression of EGF and VEGF signaling molecules and metastasis-related proteins on human salivary ACC cells orthotopically growing in nude mice. In Western blot and immunohistochemical analyses, EGFR and VEGFR-2 were presented and phosphorylated in ACC2 cells. In human parotid cancer xenografts in nude mice, EGF and VEGF signaling molecules, IL-8, and MMP-9 were expressed at markedly higher levels than in normal parotid tissues. Moreover, tumor-associated endothelial cells of this orthotopic parotid tumor expressed phosphorylated VEGFR-2 and phosphorylated Akt, which is a cell-survival protein. These data show that those biomarkers can be molecular targets for therapy of salivary ACC, which has a propensity for delayed lung metastasis.

• 대한소아치과학회지
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• 제34권3호
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• pp.438-446
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• 2007

치주인대섬유모세포들은 완전탈구 된 치아의 성공적인 재식을 위한 중요한 요소이다. 따라서, 외상으로 인해 완전탈구된 치아의 보존을 위한 보관액을 선택하는 것이 중요하다. 성장인자들과 호르몬들은 치주인대섬유모세포들의 생존을 위한 치료적 제제로 고려되고 있다. Epidermal growth factor(EGF)는 다른 조직에서 재생과 상처 치유 과정의 중요한 역할인자로 대두되고 있다. 따라서, 완전탈구 된 치아를 위한 치료적 적용을 위해 EGF의 세포 증식에 미치는 영향을 평가하였다. 또한 EGF와 tri-iodothyronine(T3)의 혼합액, EGF와 Heparin-binding epidermal growth factor-like growth factor(HB-EGF)의 혼합액이 세포 증식에 미치는 상승 효과를 평가하였다. 치주인대섬유모세포의 세포증식은 EGF 농도가 증가함에 따라 증가하였고, 10 ng/ml 농도에서 최대 세포증식을 보였다. EGF는 상처치유분석에서 상처 치유촉진과 이동성을 보여주었다. EGF에 T3와 HB-EGF를 첨가한 혼합액에서 배양한 세포는 EGF만 처리한 경우보다 세포 증식이 상승되었다. EGF와 T3 혼합액의 상승효과 기전을 유추하기 위해서 RT-PCR로 EGF 수용기의 발현을 확인하였고, T3가 EGF 수용기 발현을 증가시켰음을 확인하였다. 따라서 EGF와, EGF와 T3, EGF와 HB-EGF의 혼합액은 완전탈구된 치아의 치료에 있어 유용한 선택이 될 것이다.

• Natural Product Sciences
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• 제27권2호
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• pp.134-139
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• 2021

A new cipadesin limonoid, i.e. 3-epi-cipadonoid C (1), and a new tirucallane triterpene, i.e. hispidol B 3-palmitate (3), have been isolated from the seeds and fruit peels extract of Sandoricum koetjape, respectively. Along with these compounds the known limonoid, cipaferen G (2), and two pentacyclic triterpenes, bryonolic (4) and bryononic (5) acids, were also isolated. The strucrures of the new compounds were elucidated by the analysis of NMR and mass spectral data. Compounds 1 - 5 were evaluated as the inhibitor of receptor tyrosine kinases (EGFR, Epidermal Growth Factor Receptor; HER2, HER4, Human Epidermal growth factor Receptor 2, -4; IGFR, Insulin-like Growth Factor Receptor; InsR, Insulin Receptor; KDR, Kinase insert Domain Receptor; PDGFRα, and PDGFRβ, Platelet-Derived Growth Factor Receptor-α and -β). The results showed only 1 and 3 that have weak activity against InsR.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5647-5654
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• 2015

Gall bladder cancer (GBC) is a gastro-intestinal cancer with high prevalence among north Indian women. Platelet derived growth factor-B (PDGFB) and human epidermal growth factor receptor-2 (HER2) may play roles in the etiology of GBC through the inflammation-hyperplasia-dysplasia-carcinoma pathway. To study the association of PDGFB and HER2 polymorphisms with risk of GBC, 200 cases and 300 controls were considered. PDGFB +286A>G and +1135A>C polymorphisms were investigated with an amplification refractory mutation system and the HER2 $Ile^{655}Val$ polymorphism by restriction fragment length polymorphism. Significant risk associations for PDGFB +286 GG (OR=5.25) and PDGFB +1135 CC (OR=3.19) genotypes were observed for GBC. Gender wise stratification revealed susceptibility for recessive models of PDGFB +1135A>C (OR=3.00) and HER2 $Ile^{655}Val$ (OR=2.52) polymorphisms among female GBC cases. GBC cases with gall stones were predisposed to homozygous +286 GG and +1135 CC genotypes. Significant risk associations were found for ACIle (OR=1.48), GAVal (OR=1.70), GAIle (OR=2.00) haplotypes with GBC cases and GCIle haplotype with female GBC cases (OR=10.37, P=<0.0001). Pair-wise linkage disequilibrium revealed negative associations among variant alleles. On multi-dimensional reduction analysis, a three factor model revealed significant gene-gene interaction for PDGFB +286A>G, PDGFB +1135A>C and HER2 Ile165Val SNPs with GBC. Protein-protein interaction showed significant association of PDGFB and HER2 with the epidermal growth factor receptor signaling pathway.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제31권1호
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• pp.8-17
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• 2009

Purpose: We determined the therapeutic effect of an epidermal growth factor receptor (EGFR)-specific monoclonal antibody (mAb), cetuximab (Erbitux) on the growth of oral squamous cell carcinoma (OSCC) xenografted in athymic nude mice. Experimental Design: We induced subcutaneous tumors by inoculating human tumor cell suspension into the right flank of nude mice. Nude mice with subcutaneous tumors were randomized to receive cetuximab alone, paclitaxel alone, cetuximab plus paclitaxel, or a placebo (control). Antitumor mechanisms of cetuximab were determined by immunohistochemical and apoptosis assays. Results: Cetuximab, paclitaxel, and cetuximab/paclitaxel combined therapy resulted in 50%, 52%, 67% in vivo inhibition of tumor proliferation, respectively. Tumors of mice treated with cetuximab plus paclitaxel demonstrated decreased PCNA-positive tumor cells and increased apoptotic tumor cells, which slowed growth of the murine tumors. Conclusion: These data show that EGFR can be a molecular target for the treatment of OSCC. And combination therapy with cetuximab and paclitaxel warrants further clinical study.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제36권3호
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• pp.177-185
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• 2010

Introduction: Epidermal growth factor receptor (EGFR) is expressed in human epithelial tumors including salivary cancers, and known to be correlated with tumor progression and poor clinical courses in some epithelial tumors. In this study, we determined the therapeutic effect of the anti-EGFR monoclonal antibody Erbitux (C225, cetuximab) in combination with the DNA topoisomerase I inhibitor irinotecan (CPT-11) on human salivary adenoid cystic carcinoma (SACC) cells growing in nude mice. Materials and Methods: At first, immunocytochemical analysis for the expression of EGFR and phosphorylated EGFR (pEGFR) on a human salivary ACC cell line (ACC3). To determine the in vivo effects of Erbitux and CPT-11, nude mice with orthotopic parotid tumors were randomized to receive intraperitoneal Erbitux (1 mg) two times per week, intraperitoneal Irinotecan (50 mg/kg) once per week, Erbitux plus CPT-11, or placebo. (control) Tumor volume and weight were measured. And mechanisms of in vivo activity of Erbitux and/or CPT-11 were determined by immunohistochemical/ immunofluorescent analyses. Results: Immunocytochemical staining of ACC3 demonstrated that EGFR was expressed and phosphorylated. CPT-11 inhibited ACC tumor growth in nude mice. Tumors of mice treated with CPT-11 and CPT-11 plus Erbitux exhibited increased tumor cell apoptosis and decreased microvessel density, which correlated with a decrease in the tumor volume in nude mice. But, CPT-11 seems not to be synergistic with Erbitux in our ACC3 model system. Conclusion: These results suggest that anti-EGFR monoclonal antibody and the DNA topoisomerase I inhibitor will be effective in the treatment of recurred or metastatic lesions of salivary ACC.

• Journal of Gastric Cancer
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• 제4권4호
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• pp.268-271
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• 2004

Purpose: Most gastrointestinal stromal tumors (GISTs) have gain-of-function mutations of the KIT or the platelet-derived growth factor receptor alpha (PDGFRA) genes, but approximately $10\%$ of the GISTs are wild types for both the KIT and the PDGFRA genes. The purpose of this study was to investigate the possibility that epidermal growth factor receptor (EGFR) gene mutation might be responsible for the pathogenesis of GIST. Materials and Methods: We analyzed the EGFR gene in 60 GISTs for the detection of somatic mutations by using the polymerase chain reaction (PCR), the single strand conformation polymorphism (SSCP), and DNA sequencing in exon 18, 19, and 21 encoding the kinase domain. Results: The SSCP analysis revealed no evidence of EGFR mutations in exon 18, 19, and 21 in GISTs. Conclusion: The data indicate that the EGFR gene may not be mutated in human GIST and suggest that therapies targeting the mutated EGFR gene products might not be useful in the treatment of GISTs.